EXercise InTervention in Heart Failure (EXIT-HF)

EXercise InTervention in Heart Failure (EXIT-HF): a Randomized Controlled Trial

This is a pragmatic, non-inferiority clinical trial, enrolling heart failure patients who will be randomized to a 12-week exercise training program either centre-based or home-based with telemonitoring. The impact of this intervention will be assessed on established surrogate markers in HF such as maximal exercise capacity, plasma biomarkers and quality of life. The cost-effectiveness and overall satisfaction with the treatment will also be studied. In addition to measure the clinical and economic impact of this innovative way of delivering exercise, it is intended to unravel new molecular pathways and assess a pool of biomarkers that provide a wide mechanistic picture underlying the clinical effects of exercise.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Other: Exercise Training Program

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of HFrEF and HFpEF according to criteria of the European Society of Cardiology (2016)
2. Clinical stability for ≥ 6 weeks
3. Optimal medical treatment for ≥ 6 weeks
4. Patients that are able to understand and follow the exercise prescription
5. Written informed consent

Exclusion Criteria:

1. Patients who have undertaken cardiac rehabilitation within the past 12 months
2. Patients who have received an intracardiac defibrillator (ICD), Cardiac 3. Resynchronisation therapy (CRT) or combined CRT/ICD device implanted in the last 6 weeks
3. Inability to exercise or conditions that may interfere with exercise intervention
4. Signs of ischemia during cardiopulmonary exercise test
5. Comorbidity that may influence one-year prognosis
6. Symptomatic and/or exercise induced cardiac arrhythmia or conduction disturbances
7. Currently pregnant or intend to become pregnant in the next year
8. Expectation of receiving a cardiac transplant in the next 6 months
9. Participation in another clinical trial
10. Patients who are unable to understand the study information or unable to complete the outcome questionnaires

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Home-based exercise training; The 12-week exercise-training program will include two sessions of combined exercise training per week, performed at home	Other: Exercise Training Program; The 12-week exercise-training program will include two sessions of combined exercise training per week, performed at the hospital or at home.
Active Comparator: Clinical-based exercise training; The 12-week exercise-training program will include two sessions of combined exercise training per week, performed at the hospital	Other: Exercise Training Program; The 12-week exercise-training program will include two sessions of combined exercise training per week, performed at the hospital or at home.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak oxygen uptake (ml/kg/min)	Patients will be submitted to cardiopulmonary treadmill exercise tests at baseline and after 3 moths	Change from baseline in peak oxygen uptake (ml/kg/min) at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating number of endothelial progenitor cells, circulating endothelial cells, nitric oxide and endothelial Nitric Oxide Synthase	These markers will inform endothelial function, damage and repair	Change from baseline to 3 months
6-min walk test (6MWT) distance	Changes in distance from the 6MWT.	Change from baseline to 3 months, and to 12 months.
Health status (EQ-5D-5L)	Health status will be evaluated by the 5-level EQ-5D version (EQ-5D-5L) questionnaire. The questionnaire comprises five dimensions, each describing a different aspect of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has five response levels of severity which range from 0 (no problems) to 5 (extreme problems/ unable to do). In addition, there is a score of overall health range from 0 to 100%.	Change from baseline to 3 months, and to 12 months.
Health-related quality of life (MLHFQ)	Health-related quality of life will be evaluated by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The MLHFQ is composed of 21 questions rated on a scale from 0 (no effect) to 5 (very much). The questionnaire is scored by summation of all 21 responses, where higher scores indicate worse quality of life.	Change from baseline to 3 months, and to 12 months.
Anxiety and Depression (HADS)	Anxiety and Depression will be evaluated by the Hospital Anxiety and Depression Scale (HADS). The questionnaire is composed of 14 questions on a four-point (0-3) scale. The possible scores ranged from 0 to 21 for anxiety and 0 to 21 for depression. A score of 0 to 7 for either subscale will be regarded as being in the normal range, a score of 11 or higher indicating probable presence of the mood disorder and a score of 8 to 10 being just suggestive of the presence of the respective state.	Change from baseline to 3 months, and to 12 months.
Disutility	Individual disutility (inconvenience) perceived by patients and respective quality of life gains. Longevity to offset the exercise program disutility will be expressed in days.	Evaluate at 3th month
Physical activity (steps/day)	Physical activity will be assessed by a POLAR-M200 device with the numbers of daily steps.	Change from baseline to 3 months, and to 12 months.
Daily physical activity levels (min/day)	Daily physical activity levels it will be measure with a POLAR-M200 device. Measures will be described as time spend in light physical activity, moderate and vigorous physical activity, and spend sitting or lying (minutes per day).	Change from baseline to 3 months, and to 12 months.
Dyspnea	Dyspnea will be evaluated by the Dyspnea-12 (D-12) questionnaire. The D-12 consists of 12 descriptor items on a scale of none (0), mild (1), moderate (2), or severe (3). It provides an overall score for breathlessness severity that incorporates seven physical items and five affective items. Total scores from the D-12 range from 0 to 36, with higher scores corresponding to greater severity.	Change from baseline to 3 months, and to 12 months.
Mediterranean diet	Adherence to Mediterranean diet will be evaluated by the 14-Item Mediterranean Diet Assessment Tool (MEDAS-14). The answer to each of the 14 items is scored with 1 in the case of meeting the criteria defined as typical of this type of food (range of possible variation 0-14 points). A total score ≥10 as represent a good adherence to the Mediterranean diet.	Change from baseline to 3 months, and to 12 months.
Hand grip strength	Hand grip strength will be assessed by Jamar dynamometer (kg)	Change from baseline to to 3 and to 12 months.
Biomarkers (pg/ml)	NTproBNP and ST2 (pg/ml)	Change from baseline to 3 months
Biomarkers (mg/L)	hsCRP and Troponin (mg/L)	Change from baseline to 3 months
Concentration of plasma exosomes	Plasma exosomes will be isolated using microbead-based sorting techniques and characterized by nanoparticle tracking analysis, Western blot, and quantitative real-time polymerase chain reaction assessments	Change from baseline to 3 months
Percentage of protein aggregates	Protein aggregates (%) will be analysed using a diagonal two-dimensional (D2D) SDS-PAGE assay with mass spectrometry to identify and characterize detergent-resistant protein aggregates in plasma pre-cleared from albumin and immunoglobulin.	Change from baseline to 3 months
Cost-effectiveness of home-based exercise Vs. clinical-base exercise	Compare cost effectiveness analysis of home-based exercise Vs. clinical-base exercise. The main outcome measure for this study will be cost per quality adjusted life year (QALY)	At 12th month
Physical fitness levels evaluation	Physical fitness levels will be evaluated by the Senior Fitness test	Change from baseline to 3 and to 12 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analyses of urine proteome	Exploratory analyses in urine protein will be performed to identify novel biomarkers predictive of exercise training therapeutic response. Urine of 10 patients from each group will be analyzed using a proteomic approach combining one-dimensional gel electrophoresis with liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Generated proteomic data will be analyzed with bioinformatic tools to reveal possible biomarkers of interest, that will be further validated by immuno-approaches such as ELISA or immunoblot.	Change from baseline to 3 months

Collaborators and Investigators

• Sponsor: Centro Hospitalar do Porto
• Collaborators: Universidade do Porto; Aveiro University
• Investigators: Principal Investigator: Mário Santos, MD,PhD, Cardiology Service of Centro Hospitalar do Porto

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Heart failure; Cost-effectiveness; Maximal oxygen consumption; Home-based exercise
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2019.123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No